Antigenic variation has been suggested as a meas by which several lentiviruses, including equine infectious anemia virus (EIAV), AIDS retrovirus and visna virus, are able to persist in spite of a virus-specific host immune response. The goal of this project is to elucidate the factors important in the generation and selection of genetic and antigenic variants of EIAV with regard to the role of variation in viral persistence and the pathogensis of disease. We recovered isolates of EIAV from two early cycles of clinical disease in an experimentally infected horse. These isolates were found to be genetic variants as determined by RNase T1 resistant oligonucleotide fingerprint analysis. Furthermore, the isolates could be antigenically distinguished by antibody which bound to the surface of virus-infected cells, supporting the concept of a sequential development of antibody which recognizes emerging viral variants. However, no neutralizing antibody was detected during the early, febrile periods from which these variants were isolated. Instead, neutralizing antibody was detected later in the course of disease, but neutralizing antibody specific for the later appearing virus variant was detected prior to neutralizing antibody specific for the earlier appearing variant. These results suggested that neutralization might not be the mechanism for selection of EIAV variants. However, non-neutralizing antiviral antibody might still select for variants through recongition and elimination of certain virus-infected cells. Alternatively, the antibody specificity may be a response to, rather than a cause of, viral variation in vivo. In an attempt to more clearly define the role of antibody in the selection of viral variants, we plan to analyze the genetic and antigenic relatedness of six isolates of EIAV which we recovered from consecutive febrile periods of an experimentally infected horse.